The proangiogenic members of VEGF family and related receptors play a central role in the modulation of pathological angiogenesis. Recent insights indicate that, due to the strict biochemical and functional relationship between VEGFs and related receptors, the development of a new generation of agents able to target contemporarily more than one member of VEGFs might amplify the antiangiogenic response representing an advantage in term of therapeutic outcome. To identify molecules that are able to prevent the interaction of VEGFs with related receptors, we have screened small molecule collections consisting of >100 plant extracts. Here, we report the isolation and identification from an extract of the Malian plant Chrozophora senegalensis of the biflavonoid amentoflavone as an antiangiogenic bioactive molecule. Amentoflavone can to bind VEGFs preventing the interaction and phosphorylation of VEGF receptor 1 and 2 (VEGFR-1,VEGFR-2) and to inhibit endothelial cell migration and capillary-like tube formation induced by VEGF-A or placental growth factor 1 (PlGF-1) at low μm concentration. In vivo, amentoflavone is able to inhibit VEGF-A-induced chorioallantoic membrane neovascularization as well as tumor growth and associated neovascularization, as assessed in orthotropic melanoma and xenograft colon carcinoma models. In addition structural studies performed on the amentoflavone·PlGF-1 complex have provided evidence that this biflavonoid effectively interacts with the growth factor area crucial for VEGFR-1 receptor recognition. In conclusion, our results demonstrate that amentoflavone represents an interesting new antiangiogenic molecule that is able to prevent the activity of proangiogenic VEGF family members and that the biflavonoid structure is a new chemical scaffold to develop powerful new antiangiogenic molecules.
Tarallo, V., Lepore, L., Marcellini, M., Dal Piaz, F., Tudisco, L., Ponticelli, S., et al. (2011). The biflavonoid amentoflavone inhibits neovascularization preventing the activity of proangiogenic vascular endothelial growth factors. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 286(22), 19641-19651 [10.1074/jbc.M110.186239].
The biflavonoid amentoflavone inhibits neovascularization preventing the activity of proangiogenic vascular endothelial growth factors
ORLANDI, AUGUSTO;
2011-06-03
Abstract
The proangiogenic members of VEGF family and related receptors play a central role in the modulation of pathological angiogenesis. Recent insights indicate that, due to the strict biochemical and functional relationship between VEGFs and related receptors, the development of a new generation of agents able to target contemporarily more than one member of VEGFs might amplify the antiangiogenic response representing an advantage in term of therapeutic outcome. To identify molecules that are able to prevent the interaction of VEGFs with related receptors, we have screened small molecule collections consisting of >100 plant extracts. Here, we report the isolation and identification from an extract of the Malian plant Chrozophora senegalensis of the biflavonoid amentoflavone as an antiangiogenic bioactive molecule. Amentoflavone can to bind VEGFs preventing the interaction and phosphorylation of VEGF receptor 1 and 2 (VEGFR-1,VEGFR-2) and to inhibit endothelial cell migration and capillary-like tube formation induced by VEGF-A or placental growth factor 1 (PlGF-1) at low μm concentration. In vivo, amentoflavone is able to inhibit VEGF-A-induced chorioallantoic membrane neovascularization as well as tumor growth and associated neovascularization, as assessed in orthotropic melanoma and xenograft colon carcinoma models. In addition structural studies performed on the amentoflavone·PlGF-1 complex have provided evidence that this biflavonoid effectively interacts with the growth factor area crucial for VEGFR-1 receptor recognition. In conclusion, our results demonstrate that amentoflavone represents an interesting new antiangiogenic molecule that is able to prevent the activity of proangiogenic VEGF family members and that the biflavonoid structure is a new chemical scaffold to develop powerful new antiangiogenic molecules.Campo DC | Valore | Lingua |
---|---|---|
dc.authority.academicField2000 | Settore MED/08 - ANATOMIA PATOLOGICA | en |
dc.authority.ancejournal | THE JOURNAL OF BIOLOGICAL CHEMISTRY | - |
dc.authority.isicrui | 06 - Scienze mediche | en |
dc.authority.isicrui | Oncogenesi e Ricerca sul Cancro | en |
dc.authority.people | Tarallo, V | en |
dc.authority.people | Lepore, L | en |
dc.authority.people | Marcellini, M | en |
dc.authority.people | Dal Piaz, F | en |
dc.authority.people | Tudisco, L | en |
dc.authority.people | Ponticelli, S | en |
dc.authority.people | Lund, F | en |
dc.authority.people | Roepstorff, P | en |
dc.authority.people | ORLANDI, AUGUSTO | en |
dc.authority.people | Pisano, C | en |
dc.authority.people | De Tommasi, N | en |
dc.authority.people | De Falco, S. | en |
dc.cilea.antefix | yes | it |
dc.cilea.autoapproval | Questa scheda non e' stata ancora verificata e potrebbe quindi contenere imprecisioni. Scheda pubblicata automaticamente il Mon Mar 12 17:57:25 CET 2012 | - |
dc.collection.id.s | e291c0df-b2a9-cddb-e053-3a05fe0aa144 | * |
dc.collection.name | 01 - Articolo su rivista | * |
dc.contributor.appartenenza | Dipartimento di Biomedicina e Prevenzione | * |
dc.contributor.appartenenza.mi | 7082 | * |
dc.contributor.area | AREA MIN. 06 - Scienze mediche | * |
dc.date.accessioned | 2012-03-12T16:57:25Z | - |
dc.date.available | 2012-03-12T16:57:25Z | - |
dc.date.issued | 2011-06-03 | - |
dc.date.submission | 2020-01-10T15:37:19Z | * |
dc.description.abstracteng | The proangiogenic members of VEGF family and related receptors play a central role in the modulation of pathological angiogenesis. Recent insights indicate that, due to the strict biochemical and functional relationship between VEGFs and related receptors, the development of a new generation of agents able to target contemporarily more than one member of VEGFs might amplify the antiangiogenic response representing an advantage in term of therapeutic outcome. To identify molecules that are able to prevent the interaction of VEGFs with related receptors, we have screened small molecule collections consisting of >100 plant extracts. Here, we report the isolation and identification from an extract of the Malian plant Chrozophora senegalensis of the biflavonoid amentoflavone as an antiangiogenic bioactive molecule. Amentoflavone can to bind VEGFs preventing the interaction and phosphorylation of VEGF receptor 1 and 2 (VEGFR-1,VEGFR-2) and to inhibit endothelial cell migration and capillary-like tube formation induced by VEGF-A or placental growth factor 1 (PlGF-1) at low μm concentration. In vivo, amentoflavone is able to inhibit VEGF-A-induced chorioallantoic membrane neovascularization as well as tumor growth and associated neovascularization, as assessed in orthotropic melanoma and xenograft colon carcinoma models. In addition structural studies performed on the amentoflavone·PlGF-1 complex have provided evidence that this biflavonoid effectively interacts with the growth factor area crucial for VEGFR-1 receptor recognition. In conclusion, our results demonstrate that amentoflavone represents an interesting new antiangiogenic molecule that is able to prevent the activity of proangiogenic VEGF family members and that the biflavonoid structure is a new chemical scaffold to develop powerful new antiangiogenic molecules. | - |
dc.description.allpeople | Tarallo, V; Lepore, L; Marcellini, M; Dal Piaz, F; Tudisco, L; Ponticelli, S; Lund, F; Roepstorff, P; Orlandi, A; Pisano, C; De Tommasi, N; De Falco, S | - |
dc.description.allpeopleoriginal | Tarallo, V; Lepore, L; Marcellini, M; Dal Piaz, F; Tudisco, L; Ponticelli, S; Lund, F; Roepstorff, P; Orlandi, A; Pisano, C; De Tommasi, N; De Falco, S | en |
dc.description.fulltext | none | en |
dc.description.fulltextoriginal | none | en |
dc.description.numberofauthors | 12 | - |
dc.identifier.citation | Tarallo, V., Lepore, L., Marcellini, M., Dal Piaz, F., Tudisco, L., Ponticelli, S., et al. (2011). The biflavonoid amentoflavone inhibits neovascularization preventing the activity of proangiogenic vascular endothelial growth factors. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 286(22), 19641-19651 [10.1074/jbc.M110.186239]. | en |
dc.identifier.doi | 10.1074/jbc.M110.186239 | en |
dc.identifier.isi | WOS:000291027700047 | - |
dc.identifier.scopus | 2-s2.0-79957590393 | - |
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dc.language.iso | eng | en |
dc.relation.firstpage | 19641 | en |
dc.relation.issue | 22 | en |
dc.relation.lastpage | 19651 | en |
dc.relation.numberofpages | 11 | en |
dc.relation.volume | 286 | en |
dc.subject.keywordseng | Vascular Endothelial Growth Factor A; Animals; Vascular Endothelial Growth Factor Receptor-2; HEK293 Cells; Humans; Vascular Endothelial Growth Factor Receptor-1; Mice; Mice, Nude; Angiogenesis Inhibitors; Neoplasm Transplantation; Biflavonoids; Phosphorylation; Xenograft Model Antitumor Assays; Transplantation, Heterologous; Neovascularization, Pathologic; Antineoplastic Agents, Phytogenic; Colonic Neoplasms | - |
dc.subject.singlekeyword | Vascular Endothelial Growth Factor A | * |
dc.subject.singlekeyword | Animals | * |
dc.subject.singlekeyword | Vascular Endothelial Growth Factor Receptor-2 | * |
dc.subject.singlekeyword | HEK293 Cells | * |
dc.subject.singlekeyword | Humans | * |
dc.subject.singlekeyword | Vascular Endothelial Growth Factor Receptor-1 | * |
dc.subject.singlekeyword | Mice | * |
dc.subject.singlekeyword | Mice | * |
dc.subject.singlekeyword | Nude | * |
dc.subject.singlekeyword | Angiogenesis Inhibitors | * |
dc.subject.singlekeyword | Neoplasm Transplantation | * |
dc.subject.singlekeyword | Biflavonoids | * |
dc.subject.singlekeyword | Phosphorylation | * |
dc.subject.singlekeyword | Xenograft Model Antitumor Assays | * |
dc.subject.singlekeyword | Transplantation | * |
dc.subject.singlekeyword | Heterologous | * |
dc.subject.singlekeyword | Neovascularization | * |
dc.subject.singlekeyword | Pathologic | * |
dc.subject.singlekeyword | Antineoplastic Agents | * |
dc.subject.singlekeyword | Phytogenic | * |
dc.subject.singlekeyword | Colonic Neoplasms | * |
dc.title | The biflavonoid amentoflavone inhibits neovascularization preventing the activity of proangiogenic vascular endothelial growth factors | en |
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dc.type.circulation | Rilevanza internazionale | en |
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dc.type.impactfactor | si | en |
dc.type.miur | 262 | en |
dc.type.publicationstatus | Pubblicato | en |
dc.type.referee | Sì, ma tipo non specificato | en |
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scopus.contributor.name | Laura | - |
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scopus.contributor.name | Claudio | - |
scopus.contributor.name | Nunziatina | - |
scopus.contributor.name | Sandro | - |
scopus.contributor.subaffiliation | Angiogenesis Lab and Stem Cell Fate Lab; | - |
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scopus.contributor.surname | Tarallo | - |
scopus.contributor.surname | Lepore | - |
scopus.contributor.surname | Marcellini | - |
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scopus.date.issued | 2011 | * |
scopus.description.abstract | The proangiogenic members of VEGF family and related receptors play a central role in the modulation of pathological angiogenesis. Recent insights indicate that, due to the strict biochemical and functional relationship between VEGFs and related receptors, the development of a new generation of agents able to target contemporarily more than one member of VEGFs might amplify the antiangiogenic response representing an advantage in term of therapeutic outcome. To identify molecules that are able to prevent the interaction of VEGFs with related receptors, we have screened small molecule collections consisting of >100 plant extracts. Here, we report the isolation and identification from an extract of the Malian plant Chrozophora senegalensis of the biflavonoid amentoflavone as an antiangiogenic bioactive molecule. Amentoflavone can to bind VEGFs preventing the interaction and phosphorylation of VEGF receptor 1 and 2 (VEGFR-1,VEGFR-2) and to inhibit endothelial cell migration and capillary-like tube formation induced by VEGF-A or placental growth factor 1 (PlGF-1) at low μM concentration. In vivo, amentoflavone is able to inhibit VEGFA-induced chorioallantoic membrane neovascularization as well as tumor growth and associated neovascularization, as assessed in orthotropic melanoma and xenograft colon carcinoma models. In addition structural studies performed on the amentoflavone· PlGF-1 complex have provided evidence that this biflavonoid effectively interacts with the growth factor area crucial for VEGFR-1 receptor recognition. In conclusion, our results demonstrate that amentoflavone represents an interesting new antiangiogenic molecule that is able to prevent the activity of proangiogenic VEGF family members and that the biflavonoid structure is a new chemical scaffold to develop powerful new antiangiogenic molecules. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. | * |
scopus.description.allpeopleoriginal | Tarallo V.; Lepore L.; Marcellini M.; Dal Piaz F.; Tudisco L.; Ponticelli S.; Lund F.W.; Roepstorff P.; Orlandi A.; Pisano C.; De Tommasi N.; De Falco S. | * |
scopus.differences | scopus.identifier.pmid | * |
scopus.differences | scopus.description.allpeopleoriginal | * |
scopus.document.type | ar | * |
scopus.document.types | ar | * |
scopus.identifier.doi | 10.1074/jbc.M110.186239 | * |
scopus.identifier.eissn | 1083-351X | * |
scopus.identifier.pmid | 21471210 | * |
scopus.identifier.pui | 361834519 | * |
scopus.identifier.scopus | 2-s2.0-79957590393 | * |
scopus.journal.sourceid | 17592 | * |
scopus.language.iso | eng | * |
scopus.relation.firstpage | 19641 | * |
scopus.relation.issue | 22 | * |
scopus.relation.lastpage | 19651 | * |
scopus.relation.volume | 286 | * |
scopus.title | The biflavonoid amentoflavone inhibits neovascularization preventing the activity of proangiogenic vascular endothelial growth factors | * |
scopus.titleeng | The biflavonoid amentoflavone inhibits neovascularization preventing the activity of proangiogenic vascular endothelial growth factors | * |
Appare nelle tipologie: | 01 - Articolo su rivista |
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